Project Summary Age-related macular degeneration (AMD) is one of the leading causes of blindness among elderly people in the United States. Standard methods of diagnosis and progression tracking are fundus camera imaging and optical coherence tomography (OCT). Using these modalities, the anatomical changes of the retina during the onset of AMD have been widely studied. However, during the early stages of the disease, it is difficult to detect subtle anatomical differences with high accuracy, leading to prolonged diagnosis and disease management. It has been recently understood that there is a correlation between the mechanical properties of the retinal tissues and the early on-set of AMD, which can aid in the diagnosis of early stage diseases. However, the retina, which is a thin membrane at the very back of the eye, is often inaccessible to mechanical testing methods and most functional imaging methods do not meet the requirements for high resolution. Therefore, there is a strong need for a minimally invasive, high resolution, and safe imaging technology that is able to diagnose and track the disease during its first stages so that early management is possible. Acoustic radiation force optical coherence elastography (ARF-OCE) is an ideal candidate for retinal imaging because of its high-resolution, high speed, and high sensitivity to both axial and lateral mechanical contrast. It uses an ultrasound transducer to generate acoustic force on the sample, which causes vibrations that are detected by OCT. This technique has been shown to work well in ex- vivo cornea and retina studies. However, in order to translate this idea to in-vivo animal studies, and eventually to clinical trials, it is necessary to address a few limitations of the current system: low sub- millimeter imaging region, instability of moving parts causing slow imaging speed, and complexity of image reconstruction. To overcome these limitations, the primary goal of this proposal is to develop an ocular elastography system using 2 unfocused moduluated ultrasound transducers. The proposed set-up will be able to obtain 3-D elastograms of a 1 cm2 region of the retina in less than 5 seconds, and requires no moving stages and image fusion. The transducer force region will be characterized using a hydrophone and through phantom studies. The elasticity of the retinal layers will be quantified by correlating the results from a frequency sweep to the resonance frequency of the sample, which has been proven to be related to the Young?s modulus. Finally, rabbit AMD models will be used to perform in-vivo experiments and track the onset of AMD over a 12-week period. The imaging results will be compared to histology. The proposed system will have high-resolution, fast imaging speeds, and fast image analysis, and offer physicians more information about the onset and progression of AMD in order to obtain a more accurate understanding of the disease. This new technology is expected to have a significant impact to early diagnosis and management of AMD.